Low-dose alemtuzumab induction in a tailored immunosuppression protocol for sensitized kidney transplant recipients

• Published in: BMC nephrology Vol. 21; no. 1; p. 178
• Main Authors: Guthoff, Martina, Berger, Kilian, Althaus, Karina, Mühlbacher, Thomas, Bakchoul, Tamam, Steurer, Wolfgang, Nadalin, Silvio, Königsrainer, Alfred, Heyne, Nils
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 13.05.2020; BioMed Central; BMC
• Subjects: Alemtuzumab; Antibodies; Antigens; Biopsy; Cell number; Collaboration; Corticosteroids; Cytomegalovirus; Dosage; Dosage and administration; Histocompatibility testing; HLA-sensitization; Immunology; Immunosuppression; Immunotherapy; Induction; Induction therapy; Infections; Kidney transplantation; Kidney transplants; Kidneys; Lymphocytes; Lymphocytes B; Maintenance immunosuppression; Monoclonal antibodies; Mycophenolate mofetil; Mycophenolic acid; Nephrology; Pancreas; Patient outcomes; Patients; Protocol; Tacrolimus; Transplants & implants; United States; Infection; Rejection; HLA-sensitization; Maintenance immunosuppression; Induction; Allograft survival; Alemtuzumab; Protocol; Kidney transplantation
• ISSN: 1471-2369; 1471-2369
• DOI: 10.1186/s12882-020-01767-z

Induction therapy is crucial in kidney transplantation and constitutes an important cornerstone for long-term allograft survival. Alemtuzumab is a depleting CD52-specific antibody with T- and B-cell activity, leading to prolonged lymphocyte depletion for up to 12 months, with profound immunosuppression and an associated risk of serious infections. Current concepts aim to optimize dosing strategies to reduce side effects. Here we present data from an ongoing centre protocol consisting of low-dose alemtuzumab induction and tailored immunosuppression in sensitized patients undergoing kidney transplantation. 10-year results of the protocol were analysed. Low-dose alemtuzumab induction consisted of a single dose of 20 mg intraoperatively, followed by tacrolimus and corticosteroids for initial immunosuppression, with mycophenolate mofetil suspended until a total lymphocyte count (TLC) >5% or 200/μl was reached. Between 01/2007 and 04/2017, 46 patients were treated in accordance with the protocol in 48 kidney transplantations. Median PRA was 43 [22-76; IQR] %; all patients had negative CDC-crossmatch prior to transplantation. Low-dose alemtuzumab was well tolerated. Median time to TLC recovery was 77 [62-127; IQR] d. Within a median follow-up of 3.3 [1.5-5.6; IQR] years, 12 (25%) patients developed BPAR, 10 of which were antibody-mediated (3 acute, 7 chronic ABMR). Death-censored 5-year allograft survival was 79.2%, with an excellent allograft function at the end of follow-up. There was no increased rate of infections, in particular viral infections. Our protocol, comprising low-dose alemtuzumab induction, initial suspension of mycophenolate mofetil and triple maintenance immunosuppression, provides excellent patient and allograft outcome in sensitized renal allograft recipients.